The long range purpose of this project is to study the mechanism of chemically induced hepatomas and ovarian tumors. We are particularly interested in the role of environmental contaminants such as the polycyclic hydrocarbons, nitroso-compounds, and N-acetylarylamines, and of antitumor agents in initiating these tumors, as well as the role of genetic predisposition in tumor development. These tumors, at various time points during their development, will be used as models for evaluating chemotherapeutic agents and other drugs which might be of therapeutic value. Topics of present interest are: (1) the role of metabolic activation, as well as the genetic control of activating enzymes, in the chemical initiation of hepatomas and ovarian tumors; (2) the time course of hepatoma and ovarian tumor formation with particular emphasis on the changing enzyme patterns as the cells become increasingly dedifferentiated; (3) isolation and characterization of premalignant cell populations in the liver.